Local interaction of prostaglandin F2α with endothelin-1 and tumor necrosis factor-α on the release of progesterone and oxytocin in ovine corpora lutea in vivo: a possible implication for a luteolytic cascade

Endothelin-1 (ET-1) and tumor necrosis factor-a (TNFa) participate in the cascade of luteolysis. Thus, in the present study the interactions of ET-1 and TNFa with prostaglandin F 2α (PGF 2α ) on the release of progesterone and oxytocin (OT) within the corpus luteum (CL) were investigated. A microdialysis system (MDS) was surgically implanted in ovine CL (one MDS line/CL; 5-10 lines/ewe) formed after super-ovulation. A 4-h perfusion with PGF 2α (0.01-1 μmol l -1 ) induced no clear effect on progesterone release, but acutely stimulated OT release in a dose-dependent manner. A perfusion of PGF 2α (1 μmol l -1 ) increased ET-1 release over a period of 12 h. Two perfusions of ET-1 (0.1 μmol l -1 ) or a perfusion of ET-1 followed by TNFa (200 ng ml -1 ) decreased progesterone release (56-64% at 36-48 h). When the CL were pre-perfused with PGF 2α (1 μmol l -1 ), two consecutive perfusions of ET-1 decreased progesterone release more rapidly. Similarly, a pre-perfusion with PGF 2α followed by consecutive perfusions of ET-1 and then TNFa rapidly decreased progesterone release, with the inhibition most pronounced (35%) at 36-48 h. The simultaneous infusion of ET-1 with PGF 2α induced a rapid decrease in progesterone release (36% at 36-48 h). In a further study, the possible second messenger systems involved in PGF 2α action on the release of progesterone, OT and ET-1 were investigated. A perfusion with 12-Otetradecanoyl-phorbol-13-acetate (TPA; 10 μmol l -1 ), A23187 (10 μmol l -1 ), or PGF 2α + A23187 increased progesterone release during infusion, but decreased it after perfusion. All treatments induced a massive release of OT during infusion, and increased ET-1 release after infusion. These results show that ET-1 is capable of suppressing progesterone release in the PGF 2α -primed ovine CL in vivo and thus ET-1 works as a local luteolysin together with PGF 2α during the process of functional luteolysis. During structural luteolysis, TNFa may interact with PGF 2α and ET-1 to cause a rapid drop in progesterone release and accelerate the process of luteolysis. This result supports the contention that ET-1 and TNFa interact with PGF 2α as local luteolytic mediators in the ewe as previously suggested.